Across genomes, a search of 39 reversible codon mappings found the reverse-complement rule best preserved; codon position and lineage shaped departures, while the pattern does not establish a unique mechanism.
Across three genomic models, residualization and permutation tests separated shared sequence predictability from model-specific regulatory signal, but the proposed ~10 kb horizon and candidate elements still need experimental validation.
A proposed reproducible workflow would compare psaA, psbA, rbcL, rpoB, and 16S across complete genomes, then reconcile gene histories with species history to estimate congruence and transfer events; no estimate has yet been reported.
The supplied material cannot quantify the remaining lab–wild difference because site-resolved counts are missing; fourfold-site conditioning plus population-structure control is required before assigning a residual to mutation or selection.
The hypothesis is biologically plausible but currently weakly supported: supplied evidence connects stress with OXPHOS and mevalonate-related programs, not Notch-mediated co-induction within Eaat1-positive glia.
Preserving amino-acid use, third-position GC, and dinucleotide frequencies would test whether reverse-complement advantage survives stronger composition controls; the experiment is proposed, not a reported result.
CRISPRi perturbation of residualized candidates within and beyond 10 kb would test whether expression changes track regulatory signal rather than raw sequence sensitivity; computational predictions still lack wet-lab confirmation.
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